Predicting Type 2 Diabetes Based on Polymorphisms From Genome-Wide Association Studies
A Population-Based Study
- Mandy van Hoek12,
- Abbas Dehghan2,
- Jacqueline C.M. Witteman2,
- Cornelia M. van Duijn23,
- André G. Uitterlinden12,
- Ben A. Oostra23,
- Albert Hofman2,
- Eric J.G. Sijbrands1 and
- A. Cecile J.W. Janssens4
- 1Department of Internal Medicine, Erasmus University Medical Center, Rotterdam, the Netherlands
- 2Department of Epidemiology and Biostatistics, Erasmus University Medical Center, Rotterdam, the Netherlands
- 3Department of Clinical Genetics, Genetic Epidemiology Unit, Erasmus University Medical Center, Rotterdam, the Netherlands
- 4Department of Public Health, Erasmus University Medical Center, Rotterdam, the Netherlands
- Corresponding author: Dr. Eric J.G. Sijbrands, e.sijbrands{at}erasmusmc.nl
Abstract
OBJECTIVE—Prediction of type 2 diabetes based on genetic testing might improve identification of high-risk subjects. Genome-wide association (GWA) studies identified multiple new genetic variants that associate with type 2 diabetes. The predictive value of genetic testing for prediction of type 2 diabetes in the general population is unclear.
RESEARCH DESIGN AND METHODS—We investigated 18 polymorphisms from recent GWA studies on type 2 diabetes in the Rotterdam Study, a prospective, population-based study among homogeneous Caucasian individuals of 55 years and older (genotyped subjects, n = 6,544; prevalent cases, n = 686; incident cases during follow-up, n = 601; mean follow-up 10.6 years). The predictive value of these polymorphisms was examined alone and in addition to clinical characteristics using logistic and Cox regression analyses. The discriminative accuracy of the prediction models was assessed by the area under the receiver operating characteristic curves (AUCs).
RESULTS—Of the 18 polymorphisms, the ADAMTS9, CDKAL1, CDKN2A/B-rs1412829, FTO, IGF2BP2, JAZF1, SLC30A8, TCF7L2, and WFS1 variants were associated with type 2 diabetes risk in our population. The AUC was 0.60 (95% CI 0.57–0.63) for prediction based on the genetic polymorphisms; 0.66 (0.63–0.68) for age, sex, and BMI; and 0.68 (0.66–0.71) for the genetic polymorphisms and clinical characteristics combined.
CONCLUSIONS—We showed that 9 of 18 well-established genetic risk variants were associated with type 2 diabetes in a population-based study. Combining genetic variants has low predictive value for future type 2 diabetes at a population-based level. The genetic polymorphisms only marginally improved the prediction of type 2 diabetes beyond clinical characteristics.
Footnotes
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Published ahead of print at http://diabetes.diabetesjournals.org on 11 August 2008.
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- Accepted August 1, 2008.
- Received March 27, 2008.
- DIABETES
